A Clarification of the Aetiology and Pathogenesis of Renal Tubular Epithelial Cell Vacuolization in Diabetic Ketoacidosis

Abstract

Diabetes mellitus is an increasingly prevalent disease amongst Western populations. A serious and potentially fatal sequela of diabetes is diabetic ketoacidosis which often relies on post-mortem examination for diagnosis in the context of unwitnessed deaths. One of the major end-organs affected by diabetes is the kidneys, thus, post-mortem examination of the kidneys serves as a major diagnostic tool. Renal tubular vacuolization represents a standard response to a variety of metabolic insults, and analysis of vacuole morphology can assist in determining the nature of the underlying metabolic derangement. The Armanni-Ebstein phenomenon refers to a pattern of renal tubular epithelial cell vacuolization noted in diabetic coma with a demonstrated relationship to the extent of hyperglycaemia. It involves a pattern of cytoplasmic clearing by a single large vacuole with luminal displacement of nuclei by intra-vacuolar glycogen. In more recent literature, the Armanni-Ebstein phenomenon has also been used to describe basal/subnuclear vacuoles containing lipids and triglycerides, thus causing confusion. However, there are limited studies surrounding basal vacuolization in renal tubular epithelial cells beyond case reports, thus, its aetiology remains largely unknown. This thesis aims to clarify the terminology surrounding patterns of renal tubular vacuolization in diabetic ketoacidosis, investigate the aetiology of basal vacuolizations in human and animal models, and further define useful markers at autopsy for significant metabolic derangements. These studies will facilitate greater consistency in the reporting of findings by pathologists,and improve the linking of specific morphological findings to underlying pathophysiological processes and diagnoses.